Post-weaning diarrhea (PWD) is frequently associated with E. coli F18 infections in piglets. However, the underlying molecular mechanism concerning the resistance of E. coli F18 in local weaned piglets in China is not clearly understood. In the present study, by a comparative analysis of the transcriptome, a-1,3-fucosyltransferase (FUT3) was evaluated as a key candidate correlated with resistance to E. coli F18 in Sutai and Meishan piglets. Functional analysis demonstrated that FUT3 acts as a key positive regulator of E. coli F18 susceptibility in newly food accustomed piglets. However, the core promoter of FUT3 was present at −500–(−206) bp (chr.2: g.73171117–g.73171616), comprising of 9 methylated CpG sites. Among these, the methylation levels of the two CpG sites (mC-3, mC-5) located in HIF1A and Sp1 transcription factor (TF) considerably associated with mRNA expression of FUT3 (p < 0.05). Our findings indicated that the methylation of mC-3 and mC-5 sites has certain inhibitory effect on FUT3 expression and promotes the resistance of E. coli F18 in piglets. The underlined study may explore FUT3 as a new candidate target in E. coli F18 infection in Chinese local weaned piglets.

Meishan is a well-established local Chinese breed known for its high fecundity, strong immune response and high meat quality. However, the molecular mechanism of immune regulation during the development of Meishan pigs still remains unclear. Here, we performed the transcriptional sequencing of spleen tissues from Meishan pigs at different development stages. In total, 10,268 lncRNAs were identified, including 1254 novel lncRNAs and 9014 known lncRNAs. Time series analysis revealed that genes of the up-regulated module were enriched in pathways associated with transport, immunity, and histone acetylation modifications, while genes of the down-regulated module were enriched in DNA metabolic process and cell cycle. Weighted gene co-expression network analysis (WGCNA) showed the functional linkage between mRNAs and lncRNAs, indicating that lncRNAs are important regulatory elements of mRNAs. Notably, a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network that contained 3 mRNAs (AKT3, CBL and PTK2B), 17 lncRNAs and 67 miRNAs were screened out, which probably plays a critical role in immune regulation of Meishan pigs. Our findings not only revealed the transcriptome profile of spleen development, but also provide novel insights into the mechanism of lncRNA-miRNA-mRNA axis in the immune response in Meishan pigs.